Motifs, Modules, and Games in Stressed Out Bacteria

1
Motifs, Modules, and Games in Stressed Out
Bacteria
Denise M. Wolf1, Amoolya Singh4, Jay
Keasling1,5, and Adam P. Arkin1,2,3 1Physical
Biosciences Division, Lawrence Berkeley National
Lab 2Howard Hughes Medical Institute
3Bioengineering, 4Computer Science, and
5Chemical Engineering Departments, University of
California Berkeley,
Project Goals
Evolutionary modules?
Switching and non-genetic diversity in
sporulating cultures

• Hypotheses
• Sequence features conserved across niches core
  function.
• Sequence features conserved within niche but not
  across niche are necessary for adaptation to that
  niche.
• Features not even conserved within a niche are
  there for competition, commensalisms or are
  spandrels.

• We use the model organism B. subtilis as a GTL
  test bed for developing tools and concepts to
  analyze stress response network dynamics,
  organization and evolution on a global scale. We
  focus on what we call the stress ubernetwork,
  the network of networks regulating sporulation,
  competence, degradative enzyme synthesis,
  antibiotic production, alternative metabolic
  pathways for phosphate, nitrogen, and
  aerobic/anaerobic respiration, and chemotaxis -
  an arsenal of fight-or-flight survival
  strategies invoked in a probabilistic fashion
  under harsh environmental conditions.
• Dynamics/Design?
• How does the network act as environmental sensor,
  signal processor, computer, and factory? What
  design features are responsible for phenotype
  switching and non-genetic diversity? How can we
  control this network?
• Topology?
• What is the structure of the ubernetwork? Is it
  modular? If so, in what sense? Evolutionary vs.
  topological vs. dynamic modularity?
• Evolution?
• How did these networks evolve? What parts of the
  network are conserved in other species with
  identical phenotypes? What parts are different?
  Why?
• The whys of behavior
• Why are stress responses controlled as they are?
  Why non-genetic diversity?

Regulatory themes
(See Pathway Evolution poster for details)
Diversification strategies as game and mutual fund
Motifs
Agonist/antagonist operon pairs (
KipIA,Rap/Phr,Soj/Spo0J)
Biphasic motif
Cascade w/feedback (phosphorelay, MAPK)
The game
Towards modular biology?
Our approach

• Evolutionary game theory can help explore why
  cells behave as they do and elucidate the design
  principles of the regulatory circuits controlling
  cellular behaviors. In this project we
  investigate diversification strategies among
  microbes. Our formulation poses cellular
  behavior as an evolutionarily stable strategy
  (ESS) in a game pitting cell against cell and
  cell against nature.

Who wins?

• With missing or faulty environmental sensors
  (unobservable environmental transitions), a
  stochastically time varying environment selects
  for randomly phase varying phenotype expression,
  if different environmental states select for
  different cell states.
• If a populations sensors can detect
  environmental transitions, but have poor
  precision in identifying new environments, the
  ESS strategy is to probabilistically diversify
  the population into different cell-state
  subpopulations upon entry into a new environment,
  a sensor-based, mixed strategy that looks very
  much like heterogeneous stress response
  deployment in B. subtilis. .

.
Future work

• B. subtilis Stress ubernetwork dynamics graph
  theoretic analysis quantification of
  environment to diversification map cross-species
  microarray data analysis games.
• DOE GTL species apply testbed tools and concepts
  to analyzing for network dynamics, organization,
  and evolution on global scale. Optimize
  bioremediation.

An emerging paradigm? Motifs function in modules
designed by evolution to play games of survival
pitting cell against cell and cell against nature.
Wolf DM, Arkin AP.
Motifs, modules and games in bacteria. Curr.
Opin. Microbiol. 2003